**5. Conclusions**

The small cohort represents a limitation of our work, due to the di fficulty to investigate NEC at its early onset. However, our data may provide neonatal departments with immediate indications to blunt NEC-1 evolution such as: i) increasing the enteral volume of nutrition, especially in the first days of life; ii) revising and reducing antibiotic therapy up to the first week of life in preterm infants.

Availability of data and materials: All data are available in the main text or the supplementary materials and via the following repositories: Sequence Read Archive (SRA) database with the assigned identifier PRJNA579480.

Ethics approval and consent to participate: This study was approved (number of the approval: DC 2016-2804) by Neonatal and Pediatric Intensive Care Unit and Neonatology Department of Purpan Hospital in Toulouse, France. The parents of the children involved in this study gave their approval by written consensus.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2077-0383/9/7/2278/s1, Figure S1: Baseline plasma characteristics in healthy vs. NEC-1 children, Figure S2: Analysis of gu<sup>t</sup> microbiota, microbiome and metabolome during NEC-1 over the first two months of life, Figure S3: A specific microbiome and metabolome exist in healthy vs. NEC-1 children over the first two months of life, Figure S4: Fecal metabolome progression over the first two months of life in healthy children, Figure S5: Maternal and child factors shaping gu<sup>t</sup> microbiota and microbiome in healthy vs. NEC-1 children, Figure S6: Maternal and child factors shaping fecal metabolome in healthy vs. NEC-1 children.

**Author Contributions:** Conceptualization, C.B. and M.S.; Data curation, C.B. and M.S.; Formal analysis, C.B. and M.S.; Funding acquisition, M.S.; Investigation, M.S.; Methodology, C.B., D.D. and M.S.; Project administration, M.S.; Resources, C.B., O.D. and S.B.; Supervision, M.S. and E.O.; Validation, M.S.; Writing—original draft, C.B. and M.S.; Writing—review & editing, C.B. and M.S. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by LONGEVIE SA, gran<sup>t</sup> to M.S. **Acknowledgments:** We thank the departments of Neonatal and Pediatric Intensive Care Unit and Neonatology of the Purpan Hospital, Toulouse, France. We also thank Cecile Canlet and the Platform MetaToul-AXIOM for the metabolomic NMR analysis.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
